tbuckley/cabot-search huggingface dataset:
Effect of obesity on airway and systemic inflammation in adults with asthma: a systematic review and meta-analysis
Authors: Hayley A Scott, Shawn HM Ng, Rebecca F McLoughlin, Sarah R Valkenborghs, Parameswaran Nair, Alexandra C Brown, Olivia R Carroll, Jay C Horvat, Lisa G Wood
Journal: Thorax (2023)

Background Obesity is associated with more severe asthma, however, the mechanisms responsible are poorly understood. Obesity is also associated with low-grade systemic inflammation; it is possible that this inflammation extends to the airways of adults with asthma, contributing to worse asthma outcomes. Accordingly, the aim of this review was to examine whether obesity is associated with increased airway and systemic inflammation and adipokines, in adults with asthma. Methods Medline, Embase, CINAHL, Scopus and Current Contents were searched till 11 August 2021. Studies reporting measures of airway inflammation, systemic inflammation and/or adipokines in obese versus non-obese adults with asthma were assessed. We conducted random effects meta-analyses. We assessed heterogeneity using the I 2 statistic and publication bias using funnel plots. Results We included 40 studies in the meta-analysis. Sputum neutrophils were 5% higher in obese versus non-obese asthmatics (mean difference (MD)=5.0%, 95% CI: 1.2 to 8.9, n=2297, p=0.01, I 2 =42%). Blood neutrophil count was also higher in obesity. There was no difference in sputum %eosinophils; however, bronchial submucosal eosinophil count (standardised mean difference (SMD)=0.58, 95% CI=0.25 to 0.91, p&lt;0.001, n=181, I 2 =0%) and sputum interleukin 5 (IL-5) (SMD=0.46, 95% CI=0.17 to 0.75, p&lt;0.002, n=198, I 2 =0%) were higher in obesity. Conversely, fractional exhaled nitric oxide was 4.5 ppb lower in obesity (MD=−4.5 ppb, 95% CI=−7.1 ppb to −1.8 ppb, p&lt;0.001, n=2601, I 2 =40%). Blood C reactive protein, IL-6 and leptin were also higher in obesity. Conclusions Obese asthmatics have a different pattern of inflammation to non-obese asthmatics. Mechanistic studies examining the pattern of inflammation in obese asthmatics are warranted. Studies should also investigate the clinical relevance of this altered inflammatory response. PROSPERO registeration number CRD42021254525.
Carbon-Based Stimuli-Responsive Nanomaterials: Classification and Application
Authors: Chen Zhao, Jun Kang, Yuwen Li, Yan Wang, Xiaoying Tang, Zhenqi Jiang
Journal: Cyborg and Bionic Systems (2023)

Carbon-based nanomaterials, including carbon nanotubes, carbon nanospheres, and carbon nanofibers, are becoming a research hotspot due to their unique structure and good mechanical, thermal, electrical, optical, and chemical properties. With the development of material synthesis technology, they can be functionalized and used in various fields such as energy, environment, and biomedicine. In particular, stimuli-responsive carbon-based nanomaterials have stood out in recent years because of their smart behavior. Researchers have applied carbon-based nanomaterials to different disease treatments based on their stimulus-response properties. In this paper, based on stimuli-responsive carbon-based nanomaterials' morphology, we categorize them into carbon nanotubes, carbon nanospheres, and carbon nanofibers according to their morphology. Then, their applications in probes, bioimaging, tumor therapy, and other fields are discussed. Finally, we address the advantages and disadvantages of carbon-based stimuli-responsive nanomaterials and discuss their future perspective.
Initial Evidence for the Efficacy of Naporafenib in Combination With Trametinib in <i>NRAS</i>-Mutant Melanoma: Results From the Expansion Arm of a Phase Ib, Open-Label Study
Authors: Filippo de Braud, Christophe Dooms, Rebecca S. Heist, Celeste Lebbe, Martin Wermke, Anas Gazzah, Dirk Schadendorf, Piotr Rutkowski, Jürgen Wolf, Paolo A. Ascierto, Ignacio Gil-Bazo, Shumei Kato, Maria Wolodarski, Meredith McKean, Eva Muñoz Couselo, Martin Sebastian, Armando Santoro, Vesselina Cooke, Luca Manganelli, Kitty Wan, Anil Gaur, Jaeyeon Kim, Giordano Caponigro, Xuân-Mai Couillebault, Helen Evans, Catarina D. Campbell, Sumit Basu, Michele Moschetta, Adil Daud
Journal: Journal of Clinical Oncology (2023)

No approved targeted therapy for the treatment of patients with neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS)-mutant melanoma is currently available.In this phase Ib escalation/expansion study (ClinicalTrials.gov identifier: NCT02974725), the safety, tolerability, and preliminary antitumor activity of naporafenib (LXH254), a BRAF/CRAF protein kinases inhibitor, were explored in combination with trametinib in patients with advanced/metastatic KRAS- or BRAF-mutant non-small-cell lung cancer (escalation arm) or NRAS-mutant melanoma (escalation and expansion arms).Thirty-six and 30 patients were enrolled in escalation and expansion, respectively. During escalation, six patients reported grade ≥3 dose-limiting toxicities, including dermatitis acneiform (n = 2), maculopapular rash (n = 2), increased lipase (n = 1), and Stevens-Johnson syndrome (n = 1). The recommended doses for expansion were naporafenib 200 mg twice a day plus trametinib 1 mg once daily and naporafenib 400 mg twice a day plus trametinib 0.5 mg once daily. During expansion, all 30 patients experienced a treatment-related adverse event, the most common being rash (80%, n = 24), blood creatine phosphokinase increased, diarrhea, and nausea (30%, n = 9 each). In expansion, the objective response rate, median duration of response, and median progression-free survival were 46.7% (95% CI, 21.3 to 73.4; 7 of 15 patients), 3.75 (95% CI, 1.97 to not estimable [NE]) months, and 5.52 months, respectively, in patients treated with naporafenib 200 mg twice a day plus trametinib 1 mg once daily, and 13.3% (95% CI, 1.7 to 40.5; 2 of 15 patients), 3.75 (95% CI, 2.04 to NE) months, and 4.21 months, respectively, in patients treated with naporafenib 400 mg twice a day plus trametinib 0.5 mg once daily.Naporafenib plus trametinib showed promising preliminary antitumor activity in patients with NRAS-mutant melanoma. Prophylactic strategies aimed to lower the incidence of skin-related events are under investigation.
Interobserver Agreement Rates on C-X-C Motif Chemokine Receptor 4–Directed Molecular Imaging and Therapy
Authors: Philipp E. Hartrampf, Aleksander Kosmala, Sebastian E. Serfling, Lena Bundschuh, Takahiro Higuchi, Constantin Lapa, Steven P. Rowe, Yohji Matsusaka, Alexander Weich, Andreas K. Buck, Ralph A. Bundschuh, Rudolf A. Werner
Journal: Clinical Nuclear Medicine (2023)

We aimed to evaluate the interobserver agreement rates in patients scanned with C-X-C motif chemokine receptor 4 (CXCR4)-directed PET/CT, including the rate of patients eligible for CXCR4-targeted radioligand therapy (RLT) based on scan results.Four independent observers reviewed 50 CXCR4-targeted [ 68 Ga]pentixafor PET/CT of patients with various solid cancers. On a visual level, the following items were assessed by each reader: overall scan impression, number of organ and lymph node (LN) metastases and number of affected organs and LN regions. For a quantitative investigation, readers had to choose a maximum of 3 target lesions, defined as largest in size and/or most intense uptake per organ compartment. Reference tissues were also quantified, including unaffected hepatic parenchyma and blood pool. Last, all observers had to decide whether patients were eligible for CXCR4-targeted RLT. Concordance rates were tested using intraclass correlation coefficients (ICCs). For interpretation, we applied the definition of Cicchetti (with 0.4-0.59 indicating fair; 0.6-0.74, good; 0.75-1, excellent agreement).On a visual level, fair agreement was achieved for an overall scan impression (ICC, 0.58; 95% confidence interval, 0.45-0.71). Organ and LN involvement (ICC, ≥0.4) demonstrated fair, whereas CXCR4 density and number of LN and organ metastases showed good agreement rates (ICC, ≥0.65). Number of affected organs and affected LN areas, however, showed excellent concordance (ICC, ≥0.76). Quantification in LN and organ lesions also provided excellent agreement rates (ICC, ≥0.92), whereas quantified uptake in reference organs provided fair concordance (ICC, ≥0.54). Again, excellent agreement rates were observed when deciding on patients eligible for CXCR4-RLT (ICC, 0.91; 95% confidence interval, 0.85-0.95).In patients scanned with CXCR4-targeted PET/CT, we observed fair to excellent agreement rates for both molecular imaging and therapy parameters, thereby favoring a more widespread adoption of [ 68 Ga]pentixafor in the clinic.
Structural Variation Cooperates with Permissive Chromatin to Control Enhancer Hijacking-Mediated Oncogenic Transcription
Authors: Giovanni Botten, Yuannyu Zhang, Kseniia Dudnyk, Yoon Jung Kim, Xin Liu, Jacob T Sanders, Aygun Imanci, Nathalie M. Droin, Hui Cao, Pranita Kaphle, Kathryn E Dickerson, Kirthi R Kumar, Mingyi Chen, Weina Chen, Eric Solary, Peter Ly, Jian Zhou, Jian Xu
Journal: Blood (2023)

Structural variants (SVs) involving enhancer hijacking can rewire chromatin topologies to cause oncogene activation in human cancers including hematologic malignancies; however, due to the lack of tools to assess their effects on gene regulation and chromatin organization, the molecular determinants for the functional output of enhancer hijacking remain poorly understood. Here, we developed a multimodal approach to integrate genome sequencing, chromosome conformation, chromatin state, and transcriptomic alteration for quantitative analysis of transcriptional effects and structural reorganization imposed by SVs in leukemic genomes. We identified known and new pathogenic SVs including recurrent t(5;14) translocations that cause the hijacking of BCL11B enhancers for the allele-specific activation of TLX3 in a subtype of pediatric leukemia. Epigenetic perturbation of SV-hijacked BCL11B enhancers impairs TLX3 transcription required for the growth of t(5;14) leukemia cells. By CRISPR engineering of patient-derived t(5;14) in isogenic leukemia cells, we uncovered a new mechanism whereby the transcriptional output of SV-induced BCL11B enhancer hijacking is dependent on the loss of DNA hypermethylation at the TLX3 promoter. Our results highlight the importance of the cooperation between genetic alteration and permissive chromatin as a critical determinant of SV-mediated oncogene activation, with implications for understanding aberrant gene transcription following epigenetic therapies in leukemia patients. Hence, leveraging the interdependency of genetic alteration on chromatin variation may provide new opportunities to reprogram gene regulation as targeted interventions in human disease.
A bispecific inhibitor of complement and coagulation blocks activation in complementopathy models via a novel mechanism
Authors: John F Andersen, Haotian Lei, Ethan C. Strayer, Tapan Kanai, Van Pham, Xiang-Zuo Pan, Patricia Hessab Alvarenga, Gloria F Gerber, Oluwatoyin A Asojo, Ivo M Francischetti, Robert A. Brodsky, Jesus G Valenzuela, Jose Ribeiro
Journal: Blood (2023)
SPECT/CT in Pleuroperitoneal Fistula Associated With Peritoneal Dialysis
Authors: María M. Rojas-Rojas, Perdomo Camilo, Ucrós Gonzalo, Patricia Bernal
Journal: Clinical Nuclear Medicine (2023)

Abstract Pleuroperitoneal fistula is a rare entity found in approximately 1.6% of patients with peritoneal dialysis. The pathophysiology is unknown, and it is usually associated with increased abdominal pressure. Upon pleural fluid analysis, a transudate with elevated glucose concentration is found, and the patients present with acute dyspnea, cough, and decrease in the ultrafiltration rate. We present the case of an 81-year-old woman with history of peritoneal dialysis presenting with recurrent pleural effusion. A peritoneal scintigraphy with 99m Tc was performed confirming the diagnosis of pleuroperitoneal fistula.
ETCM v2.0: An update with comprehensive resource and rich annotations for traditional Chinese medicine
Authors: Yanqiong Zhang, Xin Li, Yulong Shi, Tong Chen, Zhijian Xu, Ping Wang, Meng Yu, Wenjia Chen, Bing Li, Zhiwei Jing, Hong Jiang, Lu Fu, Wenjing Gao, Yanhua Jiang, Xia Du, Zipeng Gong, Weiliang Zhu, Hongjun Yang, Haiyu Xu
Journal: Acta Pharmaceutica Sinica B (2023)

Existing traditional Chinese medicine (TCM)-related databases are still insufficient in data standardization, integrity and precision, and need to be updated urgently. Herein, an Encyclopedia of Traditional Chinese Medicine version 2.0 (ETCM v2.0, http://www.tcmip.cn/ETCM2/front/#/) was constructed as the latest curated database hosting 48,442 TCM formulas recorded by ancient Chinese medical books, 9872 Chinese patent drugs, 2079 Chinese medicinal materials and 38,298 ingredients. To facilitate the mechanistic research and new drug discovery, we improved the target identification method based on a two-dimensional ligand similarity search module, which provides the confirmed and/or potential targets of each ingredient, as well as their binding activities. Importantly, five TCM formulas/Chinese patent drugs/herbs/ingredients with the highest Jaccard similarity scores to the submitted drugs are offered in ETCM v2.0, which may be of significance to identify prescriptions/herbs/ingredients with similar clinical efficacy, to summarize the rules of prescription use, and to find alternative drugs for endangered Chinese medicinal materials. Moreover, ETCM v2.0 provides an enhanced JavaScript-based network visualization tool for creating, modifying and exploring multi-scale biological networks. ETCM v2.0 may be a major data warehouse for the quality marker identification of TCMs, the TCM-derived drug discovery and repurposing, and the pharmacological mechanism investigation of TCMs against various human diseases.
Sleep apnea in school-age children living at high altitude
Authors: M. Grimm, A. Seglias, L. Ziegler, M. Mademilov, E. Isaeva, K. Tynybekov, A. Tilebalieva, N. Osmonbaeva, M. Furian, T.M. Sooronbaev, S. Ulrich, K.E. Bloch
Journal: Pulmonology (2023)

Among adults, sleep apnea is more common in highlanders than in lowlanders. We evaluated the sleep apnea prevalence in children living at high altitude compared to age-matched low-altitude controls.Healthy children, 7-14 y of age, living at 2500-3800m in the Tien Shan mountains, Kyrgyzstan, were prospectively studied in a health post at 3250m. Healthy controls of similar age living at 700-800m were studied in a University Hospital at 760m in Bishkek. Assessments included respiratory sleep studies scored according to pediatric standards, clinical examination, medical history, and the pediatric sleep questionnaire (PSQ, range 0 to 1 with increasing symptoms).In children living at high altitude (n = 37, 17 girls, median [quartiles] age 10.8y [9.6;13.0]), sleep studies revealed: mean nocturnal pulse oximetry 90% (89;91), oxygen desaturation index (ODI, >3% dips in pulse oximetry) 4.3/h (2.5;6.7), apnea/hypopnea index (AHI) total 1.7/h (1.0;3.6), central 1.6/h (1.0;3.3), PSQ 0.27 (0.18;0.45). In low-altitude controls (n=41, 17 girls, age 11.6y [9.5;13.0], between-groups comparison of age P=0.69) sleep studies revealed: pulse oximetry 97% (96;97), ODI 0.7/h (0.2;1.2), AHI total 0.4/h (0.1;1.0), central 0.3/h (0.1;0.7), PSQ 0.18 (0.14;0.31); P<0.05, all corresponding between-group comparisons.In school-age children living at high altitude, nocturnal oxygen saturation was lower, and the total and central AHI were higher compared to children living at low altitude. The greater score of sleep symptoms in children residing at high altitude suggests a potential clinical relevance of the nocturnal hypoxemia and subtle sleep-related breathing disturbances.
Erratum to “B7-H3 as a Therapeutic Target in Advanced Prostate Cancer” [Eur Urol 2023;83(3):224–38]
Authors: Christina Guo, Ines Figueiredo, Bora Gurel, Antje Neeb, George Seed, Mateus Crespo, Suzanne Carreira, Jan Rekowski, Lorenzo Buroni, Jon Welti, Denisa Bogdan, Lewis Gallagher, Adam Sharp, Maria D. Fenor de la Maza, Pasquale Rescigno, Daniel Westaby, Khobe Chandran, Ruth Riisnaes, Ana Ferreira, Susana Miranda, Bianca Calì, Andrea Alimonti, Silvia Bressan, Alana H.T. Nguyen, Michael M. Shen, Jessica E. Hawley, Aleksandar Obradovic, Charles G. Drake, Claudia Bertan, Chloe Baker, Nina Tunariu, Wei Yuan, Johann S. de Bono
Journal: European Urology (2023)
Wastewater concentrations of human influenza, metapneumovirus, parainfluenza, respiratory syncytial virus, rhinovirus, and seasonal coronavirus nucleic-acids during the COVID-19 pandemic: a surveillance study
Authors: Alexandria B Boehm, Bridgette Hughes, Dorothea Duong, Vikram Chan-Herur, Anna Buchman, Marlene K Wolfe, Bradley J White
Journal: The Lancet Microbe (2023)

Respiratory disease is a major cause of morbidity and mortality; however, surveillance for circulating respiratory viruses is passive and biased. Wastewater-based epidemiology has been used to understand SARS-CoV-2, influenza A, and respiratory syncytial virus (RSV) infection rates at a community level but has not been used to investigate other respiratory viruses. We aimed to use wastewater-based epidemiology to understand community viral respiratory infection occurrence.A retrospective wastewater-based epidemiology surveillance study was carried out at a large wastewater treatment plant located in California, USA. Using droplet digital RT-PCR, we measured RNA concentrations of influenza A and influenza B viruses, RSV A and RSV B, parainfluenza (1-4) viruses, rhinovirus, seasonal coronaviruses, and metapneumovirus in wastewater solids three times per week for 17 months (216 samples) between Feb 1, 2021, and June 21, 2022. Novel probe-based RT-PCR assays for non-influenza viral targets were developed and validated. We compared viral RNA concentrations to positivity rates for viral infections from clinical specimens submitted to California Sentinel Clinical Laboratories (sentinel laboratories) to assess concordance between the two datasets.We detected RNA from all tested viruses in wastewater solids. Human rhinovirus (median concentration 4300 [0-9500] copies per gram dry weight) and seasonal human coronaviruses (35 000 [17 000-56 000]) were found at the highest concentrations. Concentrations of viral RNA correlated significantly and positively with positivity rates of associated viral diseases from sentinel laboratories (tau 0·32-0·57, p<0·0009); the only exceptions were influenza B and RSV A, which were rarely detected in wastewater solids. Measurements from wastewater indicated coronavirus OC43 dominated the seasonal human coronavirus infections whereas parainfluenza 3 dominated among parainfluenza infections during the study period. Concentrations of all tested viral RNA decreased noticeably after the omicron BA.1 surge suggesting a connection between changes in human behaviour during the surge and transmission of all respiratory viruses.Wastewater-based epidemiology can be used to obtain information on circulation of respiratory viruses at a localised, community level without the need to test many individuals because a single sample of wastewater represents the entire contributing community. Results from wastewater can be available within 24 h of sample collection, generating real time information to inform public health responses, clinical decision making, and individual behaviour modifications.CDC Foundation.
SARS-CoV-2 breakthrough infection induces rapid memory and de novo T cell responses
Authors: Marios Koutsakos, Arnold Reynaldi, Wen Shi Lee, Julie Nguyen, Thakshila Amarasena, George Taiaroa, Paul Kinsella, Kwee Chin Liew, Thomas Tran, Helen E. Kent, Hyon-Xhi Tan, Louise C. Rowntree, Thi H.O. Nguyen, Paul G. Thomas, Katherine Kedzierska, Jan Petersen, Jamie Rossjohn, Deborah A. Williamson, David Khoury, Miles P. Davenport, Stephen J. Kent, Adam K. Wheatley, Jennifer A. Juno
Journal: Immunity (2023)
Efficacy and safety of the ghrelin-O-acyltransferase inhibitor BI 1356225 in overweight/obesity: Data from two Phase I, randomised, placebo-controlled studies
Authors: Susanna Bianzano, Andrea Henrich, Lena Herich, Brigitte Kalsch, Donald Sarubbi, Friedeborg Seitz, Thomas Forst
Journal: Metabolism (2023)
A mechanism by which gut microbiota elevates permeability and inflammation in obese/diabetic mice and human gut
Authors: Sidharth P Mishra, Bo Wang, Shalini Jain, Jingzhong Ding, Jared Rejeski, Cristina M Furdui, Dalane W Kitzman, Subhash Taraphder, Christian Brechot, Ambuj Kumar, Hariom Yadav
Journal: Gut (2023)

Objective Ample evidence exists for the role of abnormal gut microbiota composition and increased gut permeability (‘leaky gut’) in chronic inflammation that commonly co-occurs in the gut in both obesity and diabetes, yet the detailed mechanisms involved in this process have remained elusive. Design In this study, we substantiate the causal role of the gut microbiota by use of faecal conditioned media along with faecal microbiota transplantation. Using untargeted and comprehensive approaches, we discovered the mechanism by which the obese microbiota instigates gut permeability, inflammation and abnormalities in glucose metabolism. Results We demonstrated that the reduced capacity of the microbiota from both obese mice and humans to metabolise ethanolamine results in ethanolamine accumulation in the gut, accounting for induction of intestinal permeability. Elevated ethanolamine increased the expression of microRNA- miR-101a-3p by enhancing ARID3a binding on the miR promoter. Increased miR-101a-3p decreased the stability of zona occludens-1 ( Zo1 ) mRNA, which in turn, weakened intestinal barriers and induced gut permeability, inflammation and abnormalities in glucose metabolism. Importantly, restoring ethanolamine-metabolising activity in gut microbiota using a novel probiotic therapy reduced elevated gut permeability, inflammation and abnormalities in glucose metabolism by correcting the ARID3a/ miR-101a / Zo1 axis. Conclusion Overall, we discovered that the reduced capacity of obese microbiota to metabolise ethanolamine instigates gut permeability, inflammation and glucose metabolic dysfunctions, and restoring ethanolamine-metabolising capacity by a novel probiotic therapy reverses these abnormalities. Trial registration number NCT02869659 and NCT03269032 .
APOA4 as a novel predictor of prognosis in Stevens-Johnson syndrome/toxic epidermal necrolysis: A proteomics analysis from two prospective cohorts
Authors: Ting Gong, Peng Zhang, Shi-Fan Ruan, Zhixun Xiao, Wen Chen, Min Lin, Qingmei Zhong, Renwei Luo, Qiuyun Xu, Jiamei Peng, Bo Cheng, Fa Chen, Lihong Chen, Wen-Hung Chung, Chao Ji
Journal: Journal of the American Academy of Dermatology (2023)
Enhanced early skin treatment for atopic dermatitis in infants reduces food allergy
Authors: Kiwako Yamamoto-Hanada, Tohru Kobayashi, Masashi Mikami, Hywel C. Williams, Hirohisa Saito, Mayako Saito-Abe, Miori Sato, Makoto Irahara, Yumiko Miyaji, Fumi Ishikawa, Kunihiko Tsuchiya, Risa Tamagawa-Mineoka, Yuri Takaoka, Yutaka Takemura, Sakura Sato, Hiroyuki Wakiguchi, Miyuki Hoshi, Osamu Natsume, Fumiya Yamaide, Miwako Seike, Yukihiro Ohya, Kumiko Morita, Eisuke Inoue, Tatsuki Fukuie, Shigenori Kabashima, Yusuke Inuzuka, Koji Nishimura, Kenji Toyokuni, Hiroya Ogita, Tomoyuki Kiguchi, Kazue Yoshida, Jumpei Saito, Hajime Hosoi, Norito Katoh, Mariko Morimoto, Koji Masuda, Makoto Kameda, Amane Shigekawa, Koji Yamasaki, Megumi Nagai, Motohiro Ebisawa, Tomoyuki Asaumi, Takaaki Itonaga, Shunji Hasegawa, Hiroki Yasudo, Mizuho Nagao, Takao Fujisawa, Ryuhei Yasuoka, Toshiharu Fujiyama, Naoki Shimojo, Taiji Nakano, Yasuto Kondo, Yuji Mori, Takahiro Kawaguchi, Masaki Futamura, Kazumitsu Sugiura, Akiyo Nagai, Sachiko Kaburagi, Hiroshi Kitazawa, Hiroshi Kido, Shoji F. Nakayama
Journal: Journal of Allergy and Clinical Immunology (2023)